MECHANISMS THAT REGULATE THE ENZYMES THAT METABOLIZE CIS UNSATURATED FATTY ACIDS

我们对PGHS-1的研究表明，Tyr自由基是由 PGHS-1的过氧化物酶活性。我们的数据表明，Tyr自由基是 而不是引发花生四烯酸的活性中间体 氧合作用。最近我们已经证明了NO与酪氨酰的反应。 用ESR表征的新自由基的转化 分析。酪氨酸基与NO的反应不会改变 前列腺素的形成和支持酪氨酸的结论 自由基不负责去除13-PRO-R-氢 启动环氧合酶反应。这些调查结果正在准备中 以供出版。一氧化氮(NO)被报道可促进前列腺素 通过直接增强PGHS活性而形成。我们发现，不是 过氧化物酶的底物，但不能增强环氧合酶 活动。此外，NO不能刺激PGHS或ALTER的表达 内毒素依赖的PGHS-2表达。我们还克隆了大鼠PGHS-1和-2 并用大鼠气管细胞(EGV-6)研究它们的表达。我们观察到 除了完整的信使核糖核酸外，还有一个异常切割的PGHS-1信使核糖核酸。 此外，我们在这些细胞中观察到TPA上调了PGHS-1的表达 在大多数细胞中，它不是由配体上调的，而是结构性的 受监管的。我们已经证明了EGF调节13-HODE的形成。 叙利亚仓鼠胚胎(SHE)细胞。

Our studies with PGHS-1 indicate that a Tyr radical is formed by the peroxidase activity of PGHS-1. Our data suggest that the Tyr radical is not the reactive intermediate that initiates arachidonic acid oxygenation. Recently we have shown that NO reacts with the tyrosyl radical converting the radical to a new radical characterized by ESR analysis. Reaction of the tyrosyl radical with NO does not alter the formation of prostaglandins and support the conclusion that the tyrosyl radical is not responsible for the removal of the 13-pro-R-hydrogen that initiates the cyclooxygenase reaction. These findings are being prepared for publication. Nitric oxide(NO) is reported to enhance prostaglandin formation by direct enhancement of PGHS activity. We found that NO is a substrate for the peroxidase but does not enhance the cyclooxygenase activity. Also, NO does not stimulate the expression of PGHS or alter LPS dependent PGHS-2 expression. We have also cloned rat PGHS-1 and -2 and studied their expression by rat tracheal cells (EGV-6). We observed an aberrantly sliced PGHS-1 mRNA in addition to the complete mRNA. Furthermore, we observed in these cells that TPA up-regulated PGHS-1 which in most cells is not upregulated by ligands but constitutively regulated. We have shown that EGF regulates the formation of 13-HODE in Syrian hamster embryo (SHE) cells.